The following studies are proposed: 1. Determine the effect of morphine and naloxone in relation to each other on the accumulation of H3-l-lysine into various neurons in the rat brain. 2. Investigate the possibility that the two new protein bands observed in the CSF of heroin addicts can be detected in the CSF of rats or some other laboratory animal. If these two electrophoretically detected proteins are found to be present, we intend to evaluate the effects of tolerance and withdrawal and to attempt to characterize the protein. 3. We plan to extend earlier EM studies which demonstrated whorled bodies of smooth endoplasmic reticulum in arcuate nucleus cells in animals treated with morphine for at least a month, in animals undergoing withdrawal and in animals pretreated with the antagonist, naloxone. 4. An autoradiographic study of the effects of morphine on incorporation of labeled lysine into regenerating neurons is planned and will be undertaken by one of my graduate students. 5. Another graduate student investigation will extend our preliminary observations on prenatal treatment of rats with methadone in relation to growth and in particular in relation to the emergence of the aminergic transmitter systems. 6. We further plan to extend our recent obsevations on the immunofluorescent detection of methadone in neurons to determine if what we observe represents stereospecific binding. We also plan to evaluate the brains of neonates subjected to methadone prenatally to determine to what degree the drug reaches the neurons after transplacental transport, whether the distribution is the same as in the adult and whether it is stereospecific.